3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-acetyl-β-D-glucopyranoside)

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-acetyl-β-D-glucopyranoside)
• 英文别名: [(2R,3S,4S,5R,6S)-6-[2-[3-(1-benzofuran-5-yl)propanoyl]-3-hydroxy-5-methylphenoxy]-3,4,5-trihydroxyoxan-2-yl]methyl acetate
• 化学式: C₂₆H₂₈O₁₀
• 分子量: 500.502
• InChiKey: ZLUNTXLTCPGCFJ-XDXGNBCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  156
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3,5-二乙酰氧基甲苯 在 platinum on activated charcoal 2,4,6-三甲基吡啶 、 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 氢氧化钾 、 三氯化铝 、 硫酸 、 ammonium formate 、 苄基三丁基氯化铵 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 70.17h， 生成 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-acetyl-β-D-glucopyranoside)
  参考文献：
  名称：

  Na⁺-Glucose Cotransporter (SGLT) Inhibitors as Antidiabetic Agents. 4. Synthesis and Pharmacological Properties of 4‘-Dehydroxyphlorizin Derivatives Substituted on the B Ring

  摘要：

  In our studies of Na+-glucose cotransporter (SGLT) inhibitors as antidiabetic agents, a series of novel 4'-dehydroxyphlorizin derivatives substituted on the B ring was prepared and their effects on urinary glucose excretion were evaluated in rats. Introduction of only a small alkyl group at the 4'-position increased the activity, and 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-beta-D-glucopyranoside (4) showed the most potent effect. To overcome hydrolysis of compound 4 by beta-glucosidase in the digestive tract, the OH groups on the glucose moiety of compound 4 were modified. Three prodrugs (5, 42, and 55) were more potent than the parent compound 4 by oral administration, and finally 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-methoxycarbonyl-beta-D-glucopyranoside) (5) was selected as a new promising candidate. Compound 5 was metabolized mainly by liver esterase to the active form (4), which was about 10 times more potent than 5 in inhibiting SGLT. In oral glucose tolerance test in db/db mice, compound 5 dose-dependently suppressed the elevation of glucose levels. Single administration of 5 reduced hyperglycemia concurrently with increase of glucose excretion into urine in diabetic KK-A(y) mice. Furthermore, compound 5 suppressed the elevation of blood glucose levels but did not lower it below the normal level even in fasted conditions in KK-A(y) mice. Additionally, long-term treatment with 5 dose-dependently reduced hyperglycemia and HbA1c in KK-A(y) mice. These pharmacological data strongly suggest that compound 5 has a therapeutic potential in the treatment of NIDDM.

  DOI：

  10.1021/jm990175n

文献信息

• PHARMACEUTICAL COMPOSITIONS FOR TREATING FATTY LIVER DISEASE
  申请人：Kurosaki Eiji

  公开号：US20110003757A1

  公开（公告）日：2011-01-06

  The present invention provides a pharmaceutical composition useful as a therapeutic agent for fatty liver disease. A pharmaceutical composition, which comprises (1S)-1,5-anhydro-1-[5-(azulen-2-ylmethyl)-2-hydroxyphenyl]-D-glucitol or a pharmaceutically acceptable salt thereof, (1S)-1,5-anhydro-1-[3-(1-benzothiophen-2-ylmethyl)-4-fluorophenyl]-D-glucitol or a pharmaceutically acceptable salt thereof, or alternatively, (1S)-1,5-anhydro-1-[4-chloro-3-(4-ethoxybenzyl)phenyl]-D-glucitol or a pharmaceutically acceptable salt thereof, more specifically such a pharmaceutical composition for treating fatty liver disease, such as nonalcoholic fatty liver disease in one embodiment, or nonalcoholic simple fatty liver and/or nonalcoholic steatohepatitis in another embodiment.
• Na⁺-Glucose Cotransporter (SGLT) Inhibitors as Antidiabetic Agents. 4. Synthesis and Pharmacological Properties of 4‘-Dehydroxyphlorizin Derivatives Substituted on the B Ring
  作者：Kenji Tsujihara、Mitsuya Hongu、Kunio Saito、Hiroyuki Kawanishi、Kayoko Kuriyama、Mamoru Matsumoto、Akira Oku、Kiichiro Ueta、Minoru Tsuda、Akira Saito

  DOI：10.1021/jm990175n

  日期：1999.12.1

  In our studies of Na+-glucose cotransporter (SGLT) inhibitors as antidiabetic agents, a series of novel 4'-dehydroxyphlorizin derivatives substituted on the B ring was prepared and their effects on urinary glucose excretion were evaluated in rats. Introduction of only a small alkyl group at the 4'-position increased the activity, and 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-beta-D-glucopyranoside (4) showed the most potent effect. To overcome hydrolysis of compound 4 by beta-glucosidase in the digestive tract, the OH groups on the glucose moiety of compound 4 were modified. Three prodrugs (5, 42, and 55) were more potent than the parent compound 4 by oral administration, and finally 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-methoxycarbonyl-beta-D-glucopyranoside) (5) was selected as a new promising candidate. Compound 5 was metabolized mainly by liver esterase to the active form (4), which was about 10 times more potent than 5 in inhibiting SGLT. In oral glucose tolerance test in db/db mice, compound 5 dose-dependently suppressed the elevation of glucose levels. Single administration of 5 reduced hyperglycemia concurrently with increase of glucose excretion into urine in diabetic KK-A(y) mice. Furthermore, compound 5 suppressed the elevation of blood glucose levels but did not lower it below the normal level even in fasted conditions in KK-A(y) mice. Additionally, long-term treatment with 5 dose-dependently reduced hyperglycemia and HbA1c in KK-A(y) mice. These pharmacological data strongly suggest that compound 5 has a therapeutic potential in the treatment of NIDDM.